Integrins are a class of cellular receptors known to bind extracellular matrix proteins, and therefore mediate cell-cell and cell-extracellular matrix interactions, generally referred to as cell adhesion events. Although many integrins and the ligands that bind an integrin are described in the literature, the biological function of many of the integrins remains elusive. The integrin receptors constitute a family of proteins with shared structural characteristics of noncovalent heterodimeric glycoprotein complexes formed of α and β subunits, Cheresh & Mecham, eds., Integrins: Molecular and Biological Responses to the Extracellular Matrix, Academic Press, Inc., San Diego, Calif. 92101 (1994), Horton, Int. J. Exp. Pathol., 71:741–759 (1990). The specific cell adhesion roles that these integrins play in the many cellular interactions in tissues are still under investigation.
Endothelial-matrix interactions play a role during angiogenesis, the formation of new blood vessels. A cell adhesion receptor known as αvβ3 integrin is found on the surface of activated endothelial cells that participate in angiogenesis.
It is well known that angiogenesis is also a requirement for malignant tumor growth and metastasis. In the absence of angiogenesis local tumor expansion is suppressed. Also, the expression of a specific angiogenesis marker, the αvβ3 integrin, is known to correlate with tumor grade.
It has now been found that cationic liposomes bearing a non-peptidic integrin antagonist as a targeting agent can deliver nucleic acids such as genes to angiogenic blood vessels. Appropriately selected nucleic acids can suppress or increase blood vessel growth as desired, and thus provide a means for the treatment of angiogenesis dependent diseases.